Osteoarthritis (OA) is present in 40 million Americans and up to 30% of these people experience significant pain and disability. Quadricep muscle strength decline and cartilage breakdown are associated with OA related-functional impairment. Interventions that can both improve muscle strength and minimize cartilage loss would be important for preventing onset of costly, painful chronic disability. Resistance exercise has been shown to improve physical abilities and lower knee pain in patients with symptomatic knee OA; however, earlier evidence is fraught with major methodological limitations. Recent, compelling evidence suggests that eccentrically focused resistance exercise (ERX) may induce superior increases in muscle mass and leg function at a lower cardiovascular and metabolic cost compared to concentrically focused resistance exercise (CRX). Currently, there are no published studies comparing pure ERX and CRX on OA pain, cartilage turnover and physical function. Using an innovative prototype of resistance exercise equipment, our laboratory will rigorously compare two modes of resistance exercise on these variables in older adults with symptomatic knee OA. This proposed study is a randomized, single-blind controlled study of the relative efficacy of two resistance exercise protocols on knee pain, physical function and cartilage turnover in older adults with knee OA. The Primary Aim of this study is to determine if four months of ERX will reduce OA-related knee pain in older adults more than CRX or standard care (non-exercise control; CON). The primary outcome will be the change in knee pain subscale of the well-established, reliable and validated Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC Score) from baseline to month four. The Secondary Aim 1 will be to determine if ERX improves physical function and habitual physical activity more than CRX and CON by month four. Function and habitual physical activity will be assessed by a battery of tests (graded maximal walk test, six-minute walk test, stair climbing, 7-day pedometer test). Secondary Aim 2 will be to determine whether ERX will induce greater changes in cartilage biomarker turnover than CRX or CON by month four. Cartilage turnover will be assessed using a ratio of cartilage formation (C-propeptide of type II procollagen, [CPII]) to cartilage breakdown (Collagen Type II C- telopeptide [CTX-II]). Older adults (N=90; >60 years of age) with tibiofemoral knee OA will be recruited for this study. Participants will be randomly assigned to one of three study groups in equal distributions (n=30 per group). The three groups will include a non-exercise control (CON) group, a concentrically focused resistance training group (CRX; one set/ exercise, two sessions/ week) and an eccentrically focused resistance training group (ERX; one set/ exercise, two sessions/ week). Study measures will be collected at baseline and at month four. Mixed model analyses of covariance will be applied to the outcome variables of the Primary Aim and Secondary Aim 1. Analysis of covariance will be applied to the change in cartilage turnover ratios; Pearson correlations adjusted with Bonferroni correction, will be performed to find associations between training induced changes in pain, physical function and cartilage turnover. The findings from this novel study will be used to further develop optimal strengthening prescriptions to treat knee OA and prevent continued cartilage breakdown. PUBLIC HEALTH RELEVANCE: Osteoarthritis elicits quadricep muscle deficits and cartilage breakdown, both of which contribute to pain and functional impairment in the older adult. A possible method to combat these disease processes is resistance exercise training. This project will examine whether there are differential improvements in osteoarthritis symptoms, impairment and cartilage turnover using a novel eccentric resistance exercise program compared with concentric focused resistance exercise in older persons.